Terbutaline
Terbutaline.svg
Terbutaline ball-and-stick model.png
Terbutaline (top),
and (R)-(−)-terbutaline (bottom)
Clinical data
AHFS/Drugs.comMonograph
MedlinePlusa682144
Pregnancy
category
  • AU: A
  • C
Routes of
administration
Oral (tablets, oral solution), inhalational (DPI, nebulizer solution), SQ
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
Pharmacokinetic data
Protein binding25%
MetabolismGI tract (oral), liver; CYP450: unknown
Elimination half-life11–16 hours
Excretionurine 90% (60% unchanged), bile/faeces
Identifiers
  • (RS)-5-[2-(tert-Butylamino)-1-hydroxyethyl]benzene-1,3-diol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.041.244 Edit this at Wikidata
Chemical and physical data
FormulaC12H19NO3
Molar mass225.288 g·mol−1
3D model (JSmol)
ChiralityRacemic mixture
  • Oc1cc(cc(O)c1)C(O)CNC(C)(C)C
  • InChI=1S/C12H19NO3/c1-12(2,3)13-7-11(16)8-4-9(14)6-10(15)5-8/h4-6,11,13-16H,7H2,1-3H3 ☒N
  • Key:XWTYSIMOBUGWOL-UHFFFAOYSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Terbutaline, sold under the brand names Bricanyl and Marex among others, is a β2 adrenergic receptor agonist, used as a "reliever" inhaler in the management of asthma symptoms and as a tocolytic (anti-contraction medication) to delay preterm labor for up to 48 hours. This time can then be used to administer steroid injections to the mother which help fetal lung maturity and reduce complications of prematurity.[1] It should not be used to prevent preterm labor or delay labor more than 48–72 hours. In February 2011, the Food and Drug Administration began requiring a black box warning on the drug's label. Pregnant women should not be given injections of the drug terbutaline for the prevention of preterm labor or for long-term (beyond 48–72 hours) management of preterm labor, and should not be given oral terbutaline for any type of prevention or treatment of preterm labor "due to the potential for serious internal heart problems and death."[2][3]

It was patented in 1966 and came into medical use in 1970.[4] It is on the World Health Organization's List of Essential Medicines.[5]

Medical uses

Terbutaline is used as a fast-acting bronchodilator (often used as a short-term asthma treatment) and as a tocolytic[6] to delay premature labor.

As an asthma treatment, the inhaled form of terbutaline, starts working within 15 minutes and can last up to 6 hours. It is also sold as an injectable solution, an oral tablet, and as a syrup (in combination with guaifenesin).

Terbutaline is a pregnancy category C medication and is prescribed to stop contractions. After successful intravenous tocolysis, little evidence exists that oral terbutaline is effective.[7] Terbutaline as a treatment for premature labor is an off-label use not approved by the US FDA, who have warned that oral terbutaline is not effective and can cause severe heart problems or death, and while injectable terbutaline can be used for premature labor in emergency situations in a hospital setting, it should only be used for short periods of time.[8]

Side effects

Pharmacology

The tertiary butyl group in terbutaline makes it more selective for β2 receptors. Since there is no hydroxy group on position 4 of the benzene ring, the molecule is less susceptible to metabolism by the enzyme catechol-O-methyl transferase.[11]

Chemistry

Terbutaline is synthesized by brominating 3,5-dibenzyloxyacetophenone into 3,5-dibenzyloxybromoacetophenone, which is reacted with N-benzyl-N-tert-butylamine, giving a ketone intermediate. Reduction of this product with H₂ over Pd/C leads to terbutaline.[12][13][14]

Terbutaline synthesis.png

Stereochemistry

Terbutaline contains a stereocenter and consists of two enantiomers. This is a racemate, ie a 1: 1 mixture of (R) - and the (S) - form:[15]

Enantiomers of terbutaline
(R)-Terbutalin Structural Formula V1.svg

(R)-Terbutaline
(S)-Terbutalin Structural Formula V1.svg

(S)-Terbutaline

Society and culture

Athletics

As with all β2-adrenergic receptor agonists, terbutaline is on the World Anti-Doping Agency's list of prohibited drugs, except when administered by inhalation and a Therapeutic Use Exemption (TUE) has been obtained in advance.

Brand names

Brand names include Bronclyn, Brethine, Bricanyl, Brethaire, Marex, and Terbulin.

References

  1. ^ WHO. "Antenatal administration of corticosteroids for women at risk of preterm birth". WHO. Archived from the original on July 24, 2009. Retrieved 2013-03-25.
  2. ^ "Most Popular E-mail Newsletter". USA Today. 18 February 2011.[permanent dead link]
  3. ^ "Archived copy". Food and Drug Administration. Archived from the original on 2015-09-21. Retrieved 2015-09-13.((cite web)): CS1 maint: archived copy as title (link)
  4. ^ Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 542. ISBN 9783527607495.
  5. ^ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
  6. ^ Mohamed Ismail NA, Ibrahim M, Mohd Naim N, Mahdy ZA, Jamil MA, Mohd Razi ZR (September 2008). "Nifedipine versus terbutaline for tocolysis in external cephalic version". Int J Gynaecol Obstet. 102 (3): 263–6. doi:10.1016/j.ijgo.2008.04.010. PMID 18554601. S2CID 20258298.
  7. ^ Goldenberg, RL (November 2002). "High-Risk Pregnancy Series: An Expert's View". Obstetrics & Gynecology. 100 (5): 1020–1037. doi:10.1016/S0029-7844(02)02212-3. PMID 12423870. Archived from the original on 2011-07-20.
  8. ^ "FDA Drug Safety Communication: New warnings against use of terbutaline to treat preterm labor". Center for Drug Evaluation and Research. FDA. 17 February 2011. Retrieved 11 May 2021.
  9. ^ Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 7. ISBN 978-1-59541-101-3.
  10. ^ [1], 5 Minute Consult (Original Source: UpToDate "Terbutaline: Drug information").
  11. ^ "Medicinal Chemistry of Adrenergics and Cholinergics". Archived from the original on 2010-11-04.
  12. ^ Draco Lunds Farmacevtiska Aktiebolag, GB 1199630  (1967)
  13. ^ Draco Lunds Farmacevtiska Aktiebolag, BE 704932  (1968)
  14. ^ L. A. Svensson, I. K. Wetterlin, U.S. Patent 3,937,838 (1976)
  15. ^ F. v. Bruchhausen, G. Dannhardt, S. Ebel, A. W. Frahm, E. Hackenthal, U. Holzgrabe (Hrsg.): Hagers Handbuch der Pharmazeutischen Praxis: Band 9: Stoffe P-Z, Springer Verlag, Berlin, Aufl. 5, 2014, S. 804, ISBN 978-3-642-63389-8.